This invention relates to disposable tips for pipettes for transferring a volume of liquid from a supply container to microtiter plate wells or other containers.
Pipettes have long been used for transferring precise amounts of liquid from one container to another. A narrow end of a tubular pipette is filed with the desired volume of liquid, by air displacement, positive displacement or capillary action, then the volume is dispensed by positive or air displacement. Generally, a disposable plastic pipette tip is mounted on the pipette end to avoid having to clean or sterilize the pipette. The tipped pipette can be moved between the filling and dispensing stations manually or by automated equipment.
In automated pipettors, the pipette is moved to a multi-tip supply rack, the pipette end is inserted into a pipette tip which is held onto the pipette by friction. The tipped pipette is then moved to a supply well and inserted below a liquid level in the supply well. The pipette tip is filled with a precise quantity of liquid and then is moved to a well in a titer plate and dispensed. The sequence is repeated for each of the titer plate wells.
While this operation is quite rapid, increases in rapidity of performing these steps can be very beneficial where a very large number of tests are being performed, as in large scale high throughput screening, testing of potential drugs, such as receptor binding assays, in molecular biology, such as DNA sequencing and DNA fingerprinting, in immunology such as forensic blood typing and other related fields.
Devices having a number of parallel pipettes have been developed to allow simultaneous operation of the pipettes. Typical of these are the devices described by Suovaniemi et al. in U.S. Pat. No. 4,215,092 and Goodman in U.S. Pat. No. 5,343,909. While generally effective, these devices use separate pipettes and operated simultaneously, so that precise calibration filling of all tips with the desired liquid volume is more difficult. All pipettes will be filled with the same quantity of liquid, so that varying liquid quantity in a predetermined pattern among the wells across a plate is difficult. Further, the devices are complex and expensive, using a separate pipette for each well.
Thus, there is a continuing need for improved pipette apparatus that can rapidly dispense a precise volume of liquid to very small wells in a microtiter plate or the like, is simple in construction and operation, is adaptable to existing liquid handling equipment, is inexpensive, and can dispense different volumes of liquid into different wells in a predetermined pattern across a microtiter plate and can be easily and conveniently automated.
The above-noted problems, and others, are overcome in accordance with this invention by a pipette tip comprising a tubular body portion having a first end for placement over an end of a pipette with the interior of the tip first end configured to fit over the end of a pipette and be retained thereon. At least two spaced, approximately parallel, elongated legs are connected at a leg proximal end to a second end of the tubular body portion. Each leg has a coaxial channel therethrough, communicating at the leg proximal end with said tip body portion interior and having an open distal end.
The plural legs are configured to fit together into a reagent supply well of predetermined cross sectional area and to align with and individually fit within closely spaced titer wells, the titer wells having cross sectional areas less than that of the supply well. Thus, a single pipette tip mounted on a single pipette can simultaneously draw a liquid into each of the pipette tip channels from a single supply well, then simultaneously dispense the liquid from each channel into a different titer well, greatly speeding up dispensing without requiring multiple pipettes and complex handling apparatus. The system may also be used to transfer liquids among different similarly sized wells, such as between different small titer wells.
A storage rack is provided to support a plurality of pipette tips prior to use. Cooperating alignment means are provided on each pipette tip and the storage rack to assure that each tip will mount on each pipette in precisely the same predetermined alignment. This is critical, since when the pipette tip is filled with liquid and brought to the titer plate, the two or more channels must align with the pattern of wells in the titer plate to assure that the liquid is properly dispensed. In one preferred embodiment, a ridge extends from a side of the pipette tip and fits in a corresponding notch in the side of the storage rack opening holding the tip.
In many cases, all of the channel open ends will have the same diameter so that the same quantity of liquid will be dispensed into each titer well in the selected pattern. However, in one particularly preferred embodiment the tip openings for the different channels will be different. For example, with four channels of different outlet diameters the diameters may vary in cross sectional area to provide one quantity in the first well, two quantities in the second well, three quantities in the third well and four quantities in the fourth well. Similarly, the quantities dispensed by the four channels could vary to provide a variety of different quantities in different wells. Thus with drug screening tests and the like, the effectiveness of different ratios of drug to test material can be easily and automatically varied. Clearly, the tip alignment means discussed above is of critical importance with this embodiment, so that the correct amounts of test liquid will always be dispensed into the correct titer wells.
Any suitable number and spacing of tip channels may be used with correspondingly sized supply wells and correspondingly arranged and sized titer wells. With a rectangular layout of titer wells, 2, 4, 6 or more legs with channels could be used, with the legs arranged in a corresponding rectangular array. Or optimum speed and accuracy, tips with four channels are preferred, since four will be faster than two and four will fit into supply wells of reasonable size, where six or more will require much larger supply well cross sectional area. If desired, patterns other than rectangular may be used, such as hexagonal or circular patterns. However, for convenience and accuracy a rectangular pattern is preferred.